This invention relates to a novel composition containing optically pure (S)(-)-amisulpride or a pharmaceutically acceptable salt thereof.
This composition possesses antipsychotic properties useful in the treatment of positive, negative, affective or cognitive symptoms of schizophrenia, dysthymia, autism, tardive dyskinesia induced by neuroleptics, Tourette disease(tics), manic or depressive symptoms in patients with bipolar disorders, sudden attacks of delirium, migraine and drug addiction while inducing therapeutic effects at doses lower and with a higher safety ratio than the racemic mixture of amisulpride or its salts.
This invention also relates to a method of treatment utilizing this composition in the therapeutical indications described above.
Amisulpride, belonging to the benzamide series, is described in U.S. Pat. No. 4,401,822 to Thominet et al. Amisulpride is known for its antiapomorphine activity. Chemically, the (S)(-) isomer is (S)-(-)-4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-(ethylsulfonyl)-2-met hoxybenzamide, referred thereafter as (S)(-)-amisulpride.
At the present time, amisulpride is available only as a racemic mixture, hereinafter called (R,S)-amisulpride. (R,S)-Amisulpride is mainly used in the treatment of acute and chronic schizophrenic disorders, in which positive symptoms (such as delusions, hallucinations, thought disorders) and/or negative symptoms (such as blunted affect, emotional and social withdrawal) are prominent. More particularly (R,S)-amisulpride is used for treating patients having predominant primary negative symptoms. (R,S)-Amisulpride is also used in the treatment of depressive disorders such as dysthimia.
Pharmacological profile of (R,S)-amisulpride is well described in H.Schoemaker et al., The Journal of Pharmacology and Experimental Therapeutics, 280 (1997), 83-97 and Gh. Perrault et al., The Journal of Pharmacology and Experimental Therapeutics, 280 (1997), 73-82. In particular, it is reported how this pharmacological profile is distinct from that of classical neuroleptics such as haloperidol and from that of another benzamide, remoxipride. It is characterizd by a preferential blockade of D.sub.2 and D.sub.3 receptors with presynaptic and limbic selectivity.
According to these properties (R,S)-amisulpride has certain advantages over other antipsychotics (neuroleptic agents). (R,S)-amisulpride shows a clinical efficacy against negative, positive, affective or cognitive symptoms of schizophrenia, a low propensity to produce extrapyramidal side effects and a good general tolerance.